•Extensive overview on pattern classification and stratification studies in ASD.•Compares pattern classification and stratifications approaches head-on.•Presents potential future directions for both ...approaches in ASD research.•Suggest promising avenues for clinical translation of these two approaches.
Pattern classification and stratification approaches have increasingly been used in research on Autism Spectrum Disorder (ASD) over the last ten years with the goal of translation towards clinical applicability. Here, we present an extensive scoping literature review on those two approaches. We screened a total of 635 studies, of which 57 pattern classification and 19 stratification studies were included. We observed large variance across pattern classification studies in terms of predictive performance from about 60% to 98% accuracy, which is among other factors likely linked to sampling bias, different validation procedures across studies, the heterogeneity of ASD and differences in data quality. Stratification studies were less prevalent with only two studies reporting replications and just a few showing external validation. While some identified strata based on cognition and intelligence reappear across studies, biology as a stratification marker is clearly underexplored. In summary, mapping biological differences at the level of the individual with ASD is a major challenge for the field now. Conceptualizing those mappings and individual trajectories that lead to the diagnosis of ASD, will become a major challenge in the near future.
Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early ...life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Inhibitory brain activation was increased after Neurofeedback. • Successful learners showed increased inhibitory brain activation after training. • ADHD symptoms were reduced after ...Neurofeedback but not after control training.
Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of ...altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in
FKBP5
on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for
FKBP5
rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of
FKBP5
on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of
FKBP5
in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.
The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. ...However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.
Abstract
Date Presented 04/22/2023
OTs’ role in end-of-life care is misunderstood and underutilized. This qualitative descriptive analysis explores how OTs contribute to interdisciplinary hospice ...teams in a thematic analysis of interviews with nurses and social workers on hospice teams that employ OTs. The findings from this study can be used to advocate for more OT positions on interdisciplinary hospice teams.
Primary Author and Speaker: Sarah Baumeister
Contributing Authors: Cary Moore
Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) ...mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers.
Children and adolescents (
= 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response.
For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only.
Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.
•Neuroradiological findings are more common in autism spectrum disorder and tend to cluster.•Neuroradiological findings are not specific to autism spectrum disorder.•Neuroradiological findings may ...point toward developmental processes involved.•Qualitative screening of brain MRI scans complements quantitative morphometry.
Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample.
We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures.
There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis.
There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.
•First meta-analysis quantitatively summarizing relevant literature on cognitive event-related potentials (ERPs) in ADHD across the lifespan.•ADHD is associated with alterations in neurophysiological ...functioning during cognitive tasks.•On a group level, individuals with ADHD show moderate deviance mainly regarding later cognitive ERPs (P300, CNV, Pe).•These later cognitive ERPs represent a range of potential ADHD biomarkers.•Substantial heterogeneity and medium effect sizes (d < 0.6) limit the use of ERPs for clinical practice on an individual level.
The current meta-analysis summarizes relevant literature on earlier (P100, N100, P200, N200, ERN/Ne) versus later (P300, Pe, CNV) cognitive Event-Related Potential (ERP) differences between children, adolescents, and adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and without ADHD (non-ADHD). Furthermore, the heterogeneity in previous research is addressed by analyzing potentially relevant demographic and methodological moderators (age group, IQ, medication, comorbidity, task, cognitive function, modality, inter-stimulus-interval, number of electrodes). Via database search 52 relevant articles were identified including n = 1576 ADHD and n = 1794 non-ADHD. Using multilevel-models, pooled effect sizes were calculated. For earlier components, individuals with ADHD showed shorter Go-P100-latencies than non-ADHD. For later ERPs, individuals with ADHD showed smaller Cue-P300-amplitudes, longer Go-P300-latencies, smaller NoGo-P300-amplitudes, longer NoGo-P300-latencies, smaller CNV-amplitudes, and smaller Pe-amplitudes. The substantial heterogeneity identified for most of the ERP components could be explained by the demographic and methodological moderators of interest. This meta-analysis identified relevant moderate group differences (−0.32<d<−0.57), mainly regarding later cognitive ERPs. Nevertheless, results are characterized by substantial heterogeneity and the moderate effect sizes (d<0.6) limit the use for clinical application.
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